RT Journal Article
SR Electronic
T1 Clump sequencing exposes the spatial expression programs of intestinal secretory cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.05.237917
DO 10.1101/2020.08.05.237917
A1 Manco, Rita
A1 Averbukh, Inna
A1 Porat, Ziv
A1 Halpern, Keren Bahar
A1 Amit, Ido
A1 Itzkovitz, Shalev
YR 2020
UL http://biorxiv.org/content/early/2020/08/06/2020.08.05.237917.abstract
AB Single-cell RNA sequencing combined with spatial information on landmark genes enables reconstruction of spatially-resolved tissue cell atlases. However, such approaches are challenging for rare cell types, since their mRNA contents are diluted in the spatial transcriptomics bulk measurements used for landmark gene detection. In the small intestine, enterocytes, the most common cell type, exhibit zonated expression programs along the crypt-villus axis, but zonation patterns of rare cell types such as goblet and tuft cells remain uncharacterized. Here, we present ClumpSeq, an approach for sequencing small clumps of attached cells. By inferring the crypt-villus location of each clump from enterocyte landmark genes, we establish spatial atlases for all epithelial cell types in the small intestine. We uncover immune-modulatory programs in villus tip goblet and tuft cells and heterogeneous migration patterns of enteroendocrine cells. ClumpSeq can be applied for reconstructing spatial atlases of rare cell types in other tissues and tumors.Competing Interest StatementThe authors have declared no competing interest.